Kava (Piper methysticum) in the United States: the quiet rise of a substance with often subtle effects.

Background: Piper methysticum, commonly called kava, has long been consumed in beverage form in the Pacific Islands. Kava use in the US has slowly increased since the 1990s, but is not assessed in major epidemiological surveys.Objectives: To analyze social-media posts about kava from current, past, and prospective users, for motivations, patterns of co-use, and effects.Methods: Text from Reddit posts, and accompanying metadata, were collected and thematically coded by two independent raters.Results: 423 posts were collected, spanning January 2006 through December 2021. Of the 1,211 thematic codes applied, 1,098 (90. 7%) were concordant. Motivations for use bifurcated into self-treatment (for psychiatric or physical health conditions) and recreation; these were not mutually exclusive. Kava was rarely considered strongly euphoriant, but was valued as an anxiolytic. Kava was frequently used with other substances, most commonly kratom. Kava was used at lower doses for self-treatment than for other purposes (pseudo-R2 = 0.11). Undesirable effects (gastrointestinal upset, fatigue) were mentioned, though less often than benefits. Hepatotoxicity, reported elsewhere as a rare, non-dose-related risk, was disputed on the basis of its not having been experienced by those posting.Conclusion: Kava appears to be conceptualized among Reddit posters as an anxiolytic with few risks or adverse effects. As it grows in popularity, especially among people who use other drugs that are more liable to misuse or addiction, it should be assessed in probability samples (i.e. in the major national drug surveys) and clinical practice for its risks, potential benefits, and possible drug-drug interactions.

Kratom use as more than a "self-treatment".

Background: Mitragyna speciosa (kratom) is increasingly used in the United States for its pharmacological effects. Kratom's relative novelty makes for a dynamic situation, such that use motivations are not firmly established and may be changing. Investigators and clinicians require frequent updates on kratom trends.Objectives: To assess the current state of kratom-use initiation, sourcing, motivations, preference, conceptualizations, and perceived stigma, using survey responses from current and former users.Methods: Between April-May 2021 we recontacted 289 respondents who reported lifetime kratom use (on an unrelated survey) to answer kratom-specific questions.Results: The sample (N=129) was majority female (51.9%) and white (71.9%). Most (69.0%) reported first trying kratom after 2015. Mean age of use initiation (29.9 years) was older than for other substances, including opioids. Kratom ranked as a preferred substance by 48.5%. The strongest drug association with past-year kratom use was vaped nicotine (OR=3.31,95% CI 1.23-8.88). Use was less likely among those prescribed buprenorphine in the past year (OR=0.03, CI 0.01-0.28). Past-month cannabis use (OR=4.18,CI 1.80-9.72) had the strongest association with past-month kratom use. Over 40 use motivations were endorsed, many (but not all) supporting the "self-treatment" narrative of kratom use, including use as an opioid, alcohol, or stimulant substitute. Treatment shortfalls were associated with decisions to try kratom.Conclusions: Kratom use motivations are diversifying, with multiple factors driving use. As sales continue to increase, the public-health, clinical, and policy responses to kratom should be grounded in rigorous bench-to-bedside scientific research. Comprehensive study of kratom is currently lacking.

Acute effects of Nitrosigine® and citrulline malate on vasodilation in young adults

BACKGROUND: Athletes are increasingly exploring ways to enhance their physical performance. Increasing blood flow to the working tissues through endothelium-dependent vasodilation is one factor athletes use to realize these results. Sports supplements such as pre-workouts tout this benefit; however, many have not been tested under laboratory conditions to examine the effects of commonly used supplements on vasodilation. Two popular supplements are Nitrosigine® and citrulline malate (CM). Thus, the purpose of this experiment was to determine the effects of Nitrosigine and CM on vasodilation using ultrasound and flow mediated dilation (FMD). METHODS: Healthy, normotensive, and physically active male (n = 16) and female (n = 8) young adults participated in the present investigation. We utilized a randomized, double-blind, within-subjects design where participants reported for three trials, each preceded by a 7-day washout period. Baseline FMD measurement was obtained for each visit, followed by consumption of one clinical dose CM (8 g), Nitrosigine (1.5 g), or dextrose placebo (8 g). Following a 60-min digestion period, FMD was repeated. Supplementation order was randomized controlling for potential order effects. RESULTS: Repeated measures ANOVA yielded a significant supplement (3) x time (2) effect (p < .001), such that Nitrosigine and CM yielded a greater improvement in FMD response than placebo. After supplementation, Nitrosigine and CM increased FMD by 31 and 34%, respectively, compared to a decrease of 2% during the placebo trial. After allometric scaling of the FMD values, supplement x time effect remained significant (p = .001) and changes were similar to non-scaled results. Nitrosigine (23%) and CM (25%) generated significantly greater allometric scaled FMD values when compared to the placebo trial (0.60%). DISCUSSION: Both Nitrisigine and CM increased endothelial-dependent vasodilation as measured by a change in FMD. Increased vasodilation leads to an increase in skeletal muscle blood flow resulting in potential improvements in exercise performance.

Comparison of vitamin D metabolites in wild and captive baboons.

Vitamin D adequacy is essential for multiple physiologic processes. With limited exposure to sunlight for vitamin D3 synthesis, captive primates are supplemented with vitamin D3 (cholecalciferol). Vitamin D metabolite data from wild primates living indigenously could suggest optimum levels. The purpose of this study was to: 1) to explore whether baboons, a speciose genus whose members have significant exposed skin, coat color variation and wide geographical distribution, mirrors the skin pigmentation-vitamin D relationship found in humans; 2) compare vitamin D metabolite levels in wild and captive members of the same or similar baboon species; and 3) apply a recently developed method currently used in humans for measuring multiple vitamin D metabolites as a panel to explore if/how these metabolites can inform us on vitamin D sufficiency. Serum samples from males of three baboon species in the wild: Papio anubis (olive baboon, dark exposed skin), P. cynocephalus (yellow baboon, brown exposed skin), and P. hamadryas (hamadryas baboon, pink exposed skin), were compared with vitamin D supplemented captive olive baboons with sun exposure. Liquid chromatography/tandem mass spectrometry (LC/MS/MS) measured vitamin D and its main metabolites. Cholecalciferol, 25 hydroxyvitamin D2&3 (25(OH)D2&3 ), and 24,25 dihydroxyvitamin D2&3 (24,25(OH)2 D2&3 ), showed significant differences by species. The levels of cholecalciferol due to supplements in the captive olive baboons did not convert to higher 25(OH)D3 while the wild olive baboons exhibited the lowest levels for both cholecalciferol and 25(OH)D3 . Further metabolic conversion of 25(OH)D3 to 24,25(OH)2 D3 indicated that all baboons had more similar conversion ratios and these were within the same range found for humans that are depicted as having adequate vitamin D levels. This study provided evidence that exposed skin color does influence vitamin D3 levels, with lower levels in darker skinned species, but these differences are eliminated in the downstream metabolite conversion indicating strong regulatory control.

Mindfulness-based interventions for adults who are overweight or obese: a meta-analysis of physical and psychological health outcomes.

OBJECTIVE: The aim of this study was to evaluate the impact of mindfulness-based interventions on psychological and physical health outcomes in adults who are overweight or obese. METHODS: We searched 14 electronic databases for randomized controlled trials and prospective cohort studies that met eligibility criteria. Comprehensive Meta-analysis software was used to compute the effect size estimate Hedge's g. RESULTS: Fifteen studies measuring post-treatment outcomes of mindfulness-based interventions in 560 individuals were identified. The average weight loss was 4.2 kg. Overall effects were large for improving eating behaviours (g = 1.08), medium for depression (g = 0.64), anxiety (g = 0.62) and eating attitudes (g = 0.57) and small for body mass index (BMI; g = 0.47) and metacognition (g = 0.38) outcomes. Therapeutic effects for BMI (g = 0.43), anxiety (g = 0.53), eating attitudes (g = 0.48) and eating behaviours (g = 0.53) remained significant when examining results from higher quality randomized control trials alone. There was no efficacy advantage for studies exceeding the median dose of 12 h of face-to-face intervention. Studies utilizing an Acceptance and Commitment Therapy approach provided the only significant effect for improving BMI (g = 0.66), while mindfulness approaches produced great variation from small to large (g = 0.30-1.68) effects across a range of psychological health and eating-related constructs. Finally, the limited longitudinal data suggested maintenance of BMI (g = 0.85) and eating attitudes (g = 0.75) gains at follow-up were only detectable in lower quality prospective cohort studies. CONCLUSIONS: Mindfulness-based interventions may be both physically and psychologically beneficial for adults who are overweight or obese, but further high-quality research examining the mechanisms of action are encouraged.

Preliminary evaluation of a brief mindfulness-based stress reduction intervention for mental health professionals.

OBJECTIVES: Mental health professionals are particularly susceptible to occupational stress; however, there are limited formal programmes to address the problem. This paper discusses the preliminary results of a brief mindfulness-based stress reduction (MBSR) programme for practising professionals in a public hospital mental health unit. METHOD: A mixed-group of nine mental health professionals participated in eight weeks of daily 15-minute MBSR training interspersed with three 30-minute education sessions developed by the authors (AD and AT). Levels of psychological distress and mindfulness skill were measured before and immediately after participation. RESULTS: Following the brief MBSR programme, quantitative and qualitative participant feedback revealed a perceived reduction in psychological distress. CONCLUSIONS: A brief MBSR programme can be incorporated into the full-time workloads of practicing mental health professionals, potentially addressing a significant unmet workplace need.

C-peptide: much more than a byproduct of insulin biosynthesis.

OBJECTIVES: During the past decade, numerous studies in both humans and animals have demonstrated that C-peptide, although not influencing blood sugar control, might play a role in preventing and potentially reversing some of the chronic complications of type 1 diabetes. The aim of this paper is to present an up-to-date review of C-peptide, focusing on its role in insulin biosynthesis and in the classification of diabetes mellitus, as well as its potential clinical applications. METHODS AND RESULTS: The relevant literature cited in the MEDLINE database shows that the measurement of C-peptide production combined with screening for the presence of islet-cell and other autoantibodies seems to exert an important role in the accurate differentiation between patients with type 1 and type 2 diabetes. Also, both experimental and clinical data provide evidence suggesting that combined replacement of insulin and C-peptide has potential therapeutic value in patients with type 1 diabetes. CONCLUSIONS: Further study in this area is warranted, but the findings that pancreas transplants promote the reversal of diabetic neuropathy and stabilization of diabetic retinopathy and that both pancreas and islet transplants lead to the reversal of diabetic nephropathy lend credence to the concept that combined replacement of insulin and C-peptide may more effectively mitigate the inexorable progression of diabetes-related complications.